Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Gastroenterology, Changhai Hospital, Shanghai, P.R. China.
Cancer Res. 2017 Dec 15;77(24):6851-6862. doi: 10.1158/0008-5472.CAN-17-0067. Epub 2017 Oct 16.
The serine/threonine kinase STK33 has been implicated in cancer cell proliferation. Here, we provide evidence of a critical role for STK33 in the pathogenesis and metastatic progression of pancreatic ductal adenocarcinoma (PDAC). STK33 expression in PDAC was regulated by the hypoxia-inducible transcription factor HIF1α. In human PDAC specimens, STK33 was overexpressed and associated with poor prognosis. Enforced STK33 expression promoted PDAC proliferation, migration, invasion, and tumor growth, whereas STK33 depletion exerted opposing effects. Mechanistic investigations showed that HIF1α regulated STK33 via direct binding to a hypoxia response element in its promoter. In showing that dysregulated HIF1α/STK33 signaling promotes PDAC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve PDAC treatment. .
丝氨酸/苏氨酸激酶 STK33 已被牵涉到癌细胞增殖中。在这里，我们提供了 STK33 在胰腺导管腺癌（PDAC）发病机制和转移进展中关键作用的证据。PDAC 中的 STK33 表达受缺氧诱导转录因子 HIF1α 的调节。在人类 PDAC 标本中，STK33 过表达且与预后不良相关。强制表达 STK33 促进 PDAC 增殖、迁移、侵袭和肿瘤生长，而 STK33 耗竭则产生相反的效果。机制研究表明，HIF1α 通过直接结合其启动子中的缺氧反应元件来调节 STK33。通过显示失调的 HIF1α/STK33 信号促进 PDAC 的生长和进展，我们的结果表明 STK33 是改善 PDAC 治疗的候选治疗靶点。
